Effect of Vitamin D Supplementation on Depression in Adults: A Systematic Review of Randomized Controlled Trials (RCTs)

Vitamin D is a nutrient potentially beneficial in the treatment of depression. The study aimed to carry out a systematic review of the studies assessing the influence of vitamin D supplementation on depression within Randomized Controlled Trials (RCTs). The systematic review was prepared on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42020155779). The peer-reviewed studies available within PubMed or Web of Science databases until September 2021 were taken into account. The number of screened records was 8514, and 8 records were included. Two independent researchers conducted screening, including, reporting, and risk of bias assessment using the revised Cochrane risk-of-bias tool for randomized trials. The included studies presented a population of patients with major depressive disorders or general depression, as well as bipolar depression or postpartum depression. The majority of included studies were conducted for 8 weeks or 12 weeks, while one study was conducted for 6 months. Within the large number of included studies, a daily dose of 1500 IU, 1600 IU, or 2800 IU was applied, while within some studies, a vitamin D dose of 50,000 IU was applied weekly or biweekly. Among applied psychological measures of depression, there were various tools. In spite of the fact that the majority of included studies (five studies) supported the positive effect of vitamin D supplementation for the psychological measure of depression, for three studies the positive influence was not supported. A medium risk of bias was indicated for six studies, while a high risk of bias was defined for only two studies, due to deviations from the intended interventions and in measurement of the outcome, as well as for one study, also arising from the randomization process and due to missing outcome data. Based on conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of the medium risk of bias, while two studies of a medium risk of bias did not support it. Taking this into account, the conducted systematic review is not a strong confirmation of the effectiveness of vitamin D supplementation in the treatment of depression.


Introduction
Depression is defined as a mood disorder causing a persistent feeling of sadness and loss of interest [1], while the depressive disorders are classified as follows: disruptive mood dysregulation disorder, major depressive disorder, persistent depressive disorder (dysthymia), premenstrual dysphoric disorder, and depressive disorder due to another medical condition [2]. The diagnosis of depression is based on assessment of nine depressive symptoms (sleeping disturbance, reduction in interest/pleasure, guilt feelings/thoughts 1. study conducted in adults; 2.
studied population of patients with depression diagnosed; 3. study presenting oral vitamin D supplementation of known dose; 4.
depression monitored within the study using a valid mental health outcome measure; 5. study described as RCT; 6. study published as an article in a peer-reviewed journal.
The exclusions were conducted based on the following exclusion criteria: 1. animal model study; 2. study presenting influence of multiple nutrients combined; 3. study conducted in subjects with any concurrent physical disease or disability; 4. study conducted in pregnant women; 5. study conducted in subjects with concurrent eating disorders; 6. study conducted in subjects with concurrent intellectual disabilities; 7. study not published in English.
The patient, intervention/exposure, comparator, outcome, and study design (PICOS) criteria are presented in Table 1.

Searching Procedure
The detailed electronic search strategy applied for the systematic review within PubMed or Web of Science databases is presented in Supplementary Table S1.
After searching databases for potentially eligible studies, duplicated records were removed, if found both within PubMed and Web of Science databases. Afterwards, potentially eligible studies were identified, while using inclusion and exclusion criteria. In order to identify eligible studies, the procedure was conducted within three stages: based on titles, based on abstracts, and based on full texts. Identification based on titles and based on abstracts were conducted using data available within PubMed and Web of Science databases. Only for the studies defined as potentially eligible, after a procedure based on title and based on abstract, the full texts were assessed. In order to obtain the full text of the study, electronic databases and libraries were searched, and if not available, the corresponding authors were asked for them. The identification within all stages was conducted by two researchers independently, but in case of disagreement, the third researcher was asked for an opinion.
The procedure of identification, screening, eligibility assessment, and including studies is presented in Figure 1.

Searching Procedure
The detailed electronic search strategy applied for the systematic review within PubMed or Web of Science databases is presented in Supplementary Table S1.
After searching databases for potentially eligible studies, duplicated records were removed, if found both within PubMed and Web of Science databases. Afterwards, potentially eligible studies were identified, while using inclusion and exclusion criteria. In order to identify eligible studies, the procedure was conducted within three stages: based on titles, based on abstracts, and based on full texts. Identification based on titles and based on abstracts were conducted using data available within PubMed and Web of Science databases. Only for the studies defined as potentially eligible, after a procedure based on title and based on abstract, the full texts were assessed. In order to obtain the full text of the study, electronic databases and libraries were searched, and if not available, the corresponding authors were asked for them. The identification within all stages was conducted by two researchers independently, but in case of disagreement, the third researcher was asked for an opinion.
The procedure of identification, screening, eligibility assessment, and including studies is presented in Figure 1.

Data Extraction Procedure and Study Assessment Procedure
After including eligible studies, they were analyzed in order to extract necessary data to describe the study and the influence of vitamin D supplementation on depression. The following data were extracted: 1. the general description of the study and studied population (including authors and year of the study; country/detailed location; studied population; period of the study);

Results
The general descriptions of the studies and studied populations within studies included to a systematic review [29][30][31][32][33][34][35][36] are presented in Table 2. The large number of included studies were conducted in Iran [29,[32][33][34], while the others were conducted in Saudi Arabia [35], China [36], the United States of America [30], or Denmark [31]. They presented a studied populations of patients with major depressive disorders [29,35] or general depression [31][32][33]36], but also bipolar depression [30] or postpartum depression [34]. The descriptions of the studied populations within studies included to a systematic review are presented in Table 3. The included studies were conducted mainly in small to medium size samples of less than 100 participants (divided into studied groups and control groups) [29][30][31][32][33][34][35], while only one study was conducted in a larger group [36]. The included studies were conducted mainly in populations of young [34] to middle-aged adults [29][30][31]33,35], but one study was conducted in a group of older patients [32]. The inclusion and exclusion criteria were based on the studied population, with vitamin D deficiency sometimes indicated within inclusion criteria [30,36] or exclusion criteria [31], depending on the study.  The observations and conclusions formulated within studies included to systematic review are presented in Supplementary Table S2, and the descriptions of the vitamin D supplementation and the assessment of depression status accompanied by summary of conclusions formulated within studies included to a systematic review are presented in Table 4. The majority of included studies were conducted for 8 weeks [29,[32][33][34] or 12 weeks [30,31,35], while one study was conducted for 6 months [36]. Within the large number of included studies, the daily dose of 1500 IU [29][30][31], 1600 IU [36], or 2800 IU was applied [31]. At the same time, within some studies, the vitamin D dose of 50,000 IU was applied weekly [32,35], or biweekly [33,34]. Among applied psychological measures of depression were various tools, such as the Beck Depression Inventory (BDI) [29,33,35], Hamilton Depression Rating Scale (HDRS) [29,36], Montgomery-Åsberg Depression Rating Scale (MADRS) [30], Hamilton Rating Scale for Depression (HAM-D17) [31], Major Depression Inventory (MDI) [31], World Health Organization-Five Well-Being Index (WHO-5) [31], Geriatric Depression Scale-15 (GDS-15) [32], and the Edinburgh Postnatal Depression Scale (EPDS) [34]. In spite of the fact that the majority of included studies (five studies) confirmed the positive effect of supplementation of vitamin D for the psychological measure of depression [29,[32][33][34][35], for three studies, the positive influence was not supported [30,31,36]. Moreover, it should be emphasized that the positive influence of vitamin D was confirmed for the studies with a shorter study duration-those conducted for 8 weeks [29,[32][33][34] and one conducted for 12 weeks [35]-while it was not confirmed for the other studies conducted for 12 weeks [30,31] and for one conducted for 6 months [36]. Last but not least, it should be mentioned that in the studies for which vitamin D deficiency was indicated within the inclusion criteria [30,36], and in those for which it was indicated within the exclusion criteria [31], the positive influence of applied vitamin D doses was not confirmed, but such confirmation was obtained only for the mixed populations. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials, is presented in Table 5. For the majority of included studies, a medium risk of bias was indicated [29][30][31][32][33][34], while for only two studies, a high risk of bias was defined [35,36] due to deviations from the intended interventions and in measurement of the outcome [35,36], as well as for one study, also arising from the randomization process and due to missing outcome data [35]. This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the selection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Ref. Domain 1 Domain 2 Domain 3 Domain 4 Domain 5
Overall Bias [29] the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not the intended interventions [30,31]. The studies for which the high risk of bias wa cated were within those supporting the positive influence of the supplementation o min D for the psychological measure of depression [35], and those not supportin However, based on the conducted assessment, it should be emphasized that there a four studies supporting the positive influence of vitamin D supplementation for th chological measure of depression of medium risk of bias [29,[32][33][34], while two s with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducte the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous c sions about influence of the supplementation of vitamin D for the psychological m of depression, as the various observations were formulated within studies, which w the intended interventions [30,31]. The studies for which the high ris cated were within those supporting the positive influence of the supp min D for the psychological measure of depression [35], and those n However, based on the conducted assessment, it should be emphasized four studies supporting the positive influence of vitamin D suppleme chological measure of depression of medium risk of bias [29,[32][33][34] with a medium risk of bias did not support it [30,31]. -Low risk of bias; -Some concerns associated with risk of bias -mains: 1-arising from the randomization process; 2-deviations from the in 3-missing outcome data; 4-measurement of the outcome; 5-selection of th

Discussion
The conducted systematic review did not allow to formulate un sions about influence of the supplementation of vitamin D for the psy of depression, as the various observations were formulated within stu the intended interventions [30,31]. The studie cated were within those supporting the positi min D for the psychological measure of depr However, based on the conducted assessment four studies supporting the positive influence chological measure of depression of medium with a medium risk of bias did not support it -Low risk of bias; -Some concerns associa mains: 1-arising from the randomization process 3-missing outcome data; 4-measurement of the

Discussion
The conducted systematic review did no sions about influence of the supplementation of depression, as the various observations wer the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not [30] medium risk of bias, this resulted mainly from the randomization process and in the selection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not medium risk of bias, this resulted mainly from the randomization process and in th lection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations the intended interventions [30,31]. The studies for which the high risk of bias was cated were within those supporting the positive influence of the supplementation of min D for the psychological measure of depression [35], and those not supporting However, based on the conducted assessment, it should be emphasized that there are four studies supporting the positive influence of vitamin D supplementation for the chological measure of depression of medium risk of bias [29,[32][33][34], while two st with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous co sions about influence of the supplementation of vitamin D for the psychological me of depression, as the various observations were formulated within studies, which wa medium risk of bias, this resulted mainly from the randomization process and in lection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviation the intended interventions [30,31]. The studies for which the high risk of bias wa cated were within those supporting the positive influence of the supplementation o min D for the psychological measure of depression [35], and those not supportin However, based on the conducted assessment, it should be emphasized that there a four studies supporting the positive influence of vitamin D supplementation for th chological measure of depression of medium risk of bias [29,[32][33][34], while two s with a medium risk of bias did not support it [30,31]. -Low risk of bias; -Some concerns associated with risk of bias -High risk of b mains: 1-arising from the randomization process; 2-deviations from the intended interve 3-missing outcome data; 4-measurement of the outcome; 5-selection of the reported res

Discussion
The conducted systematic review did not allow to formulate unambiguous c sions about influence of the supplementation of vitamin D for the psychological m of depression, as the various observations were formulated within studies, which w medium risk of bias, this resulted mainly from the randomization pr lection of the reported result [29][30][31][32][33][34], but for two studies was also due the intended interventions [30,31]. The studies for which the high ris cated were within those supporting the positive influence of the supp min D for the psychological measure of depression [35], and those n However, based on the conducted assessment, it should be emphasized four studies supporting the positive influence of vitamin D suppleme chological measure of depression of medium risk of bias [29,[32][33][34] with a medium risk of bias did not support it [30,31]. -Low risk of bias; -Some concerns associated with risk of bias -mains: 1-arising from the randomization process; 2-deviations from the in 3-missing outcome data; 4-measurement of the outcome; 5-selection of th

Discussion
The conducted systematic review did not allow to formulate un sions about influence of the supplementation of vitamin D for the psy of depression, as the various observations were formulated within stu medium risk of bias, this resulted mainly from lection of the reported result [29][30][31][32][33][34], but for t the intended interventions [30,31]. The studie cated were within those supporting the positi min D for the psychological measure of depr However, based on the conducted assessment four studies supporting the positive influence chological measure of depression of medium with a medium risk of bias did not support it -Low risk of bias; -Some concerns associa mains: 1-arising from the randomization process 3-missing outcome data; 4-measurement of the

Discussion
The conducted systematic review did no sions about influence of the supplementation of depression, as the various observations wer medium risk of bias, this resulted mainly from the randomization process and in the selection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not [31] This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the selection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not This corresponds the fact that in the indicated studies, the control group was not tr with a placebo, but was just without vitamin D treatment [35,36]. For the studies w medium risk of bias, this resulted mainly from the randomization process and in th lection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations the intended interventions [30,31]. The studies for which the high risk of bias was cated were within those supporting the positive influence of the supplementation of min D for the psychological measure of depression [35], and those not supporting However, based on the conducted assessment, it should be emphasized that there are four studies supporting the positive influence of vitamin D supplementation for the chological measure of depression of medium risk of bias [29,[32][33][34], while two st with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous co sions about influence of the supplementation of vitamin D for the psychological me of depression, as the various observations were formulated within studies, which wa This corresponds the fact that in the indicated studies, the control group was not with a placebo, but was just without vitamin D treatment [35,36]. For the studies medium risk of bias, this resulted mainly from the randomization process and in lection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviation the intended interventions [30,31]. The studies for which the high risk of bias wa cated were within those supporting the positive influence of the supplementation o min D for the psychological measure of depression [35], and those not supportin However, based on the conducted assessment, it should be emphasized that there a four studies supporting the positive influence of vitamin D supplementation for th chological measure of depression of medium risk of bias [29,[32][33][34], while two s with a medium risk of bias did not support it [30,31]. -Low risk of bias; -Some concerns associated with risk of bias -High risk of b mains: 1-arising from the randomization process; 2-deviations from the intended interve 3-missing outcome data; 4-measurement of the outcome; 5-selection of the reported res

Discussion
The conducted systematic review did not allow to formulate unambiguous c sions about influence of the supplementation of vitamin D for the psychological m of depression, as the various observations were formulated within studies, which w This corresponds the fact that in the indicated studies, the control gro with a placebo, but was just without vitamin D treatment [35,36]. Fo medium risk of bias, this resulted mainly from the randomization pr lection of the reported result [29][30][31][32][33][34], but for two studies was also due the intended interventions [30,31]. The studies for which the high ris cated were within those supporting the positive influence of the supp min D for the psychological measure of depression [35], and those n However, based on the conducted assessment, it should be emphasized four studies supporting the positive influence of vitamin D suppleme chological measure of depression of medium risk of bias [29,[32][33][34] with a medium risk of bias did not support it [30,31]. -Low risk of bias; -Some concerns associated with risk of bias -mains: 1-arising from the randomization process; 2-deviations from the in 3-missing outcome data; 4-measurement of the outcome; 5-selection of th

Discussion
The conducted systematic review did not allow to formulate un sions about influence of the supplementation of vitamin D for the psy of depression, as the various observations were formulated within stu This corresponds the fact that in the indicated with a placebo, but was just without vitamin medium risk of bias, this resulted mainly from lection of the reported result [29][30][31][32][33][34], but for t the intended interventions [30,31]. The studie cated were within those supporting the positi min D for the psychological measure of depr However, based on the conducted assessment four studies supporting the positive influence chological measure of depression of medium with a medium risk of bias did not support it -Low risk of bias; -Some concerns associa mains: 1-arising from the randomization process 3-missing outcome data; 4-measurement of the

Discussion
The conducted systematic review did no sions about influence of the supplementation of depression, as the various observations wer This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the selection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not [32] for only two studies, a high risk of bias was defined [35,36] due to deviations from the intended interventions and in measurement of the outcome [35,36], as well as for one study, also arising from the randomization process and due to missing outcome data [35]. This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the selection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not for only two studies, a high risk of bias was defined [35,36] due to deviations from the intended interventions and in measurement of the outcome [35,36], as well as for one study, also arising from the randomization process and due to missing outcome data [35]. This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the se-lection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indi-cated were within those supporting the positive influence of the supplementation of vita-min D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psy-chological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials. -Low risk of bias; -Some concerns associated with risk of bias -High risk of bias; Do-mains: 1-arising from the randomization process; 2-deviations from the intended interventions; 3-missing outcome data; 4-measurement of the outcome; 5-selection of the reported result.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclu-sions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not for only two studies, a high risk of bias was defined [35,36] due to deviations fro intended interventions and in measurement of the outcome [35,36], as well as f study, also arising from the randomization process and due to missing outcome da This corresponds the fact that in the indicated studies, the control group was not with a placebo, but was just without vitamin D treatment [35,36]. For the studies medium risk of bias, this resulted mainly from the randomization process and in lection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviation the intended interventions [30,31]. The studies for which the high risk of bias wa cated were within those supporting the positive influence of the supplementation o min D for the psychological measure of depression [35], and those not supportin However, based on the conducted assessment, it should be emphasized that there a four studies supporting the positive influence of vitamin D supplementation for th chological measure of depression of medium risk of bias [29,[32][33][34], while two s with a medium risk of bias did not support it [30,31]. -Low risk of bias; -Some concerns associated with risk of bias -High risk of b mains: 1-arising from the randomization process; 2-deviations from the intended interve 3-missing outcome data; 4-measurement of the outcome; 5-selection of the reported res

Discussion
The conducted systematic review did not allow to formulate unambiguous c sions about influence of the supplementation of vitamin D for the psychological m of depression, as the various observations were formulated within studies, which w for only two studies, a high risk of bias was defined [35,36] due to d intended interventions and in measurement of the outcome [35,36], study, also arising from the randomization process and due to missing This corresponds the fact that in the indicated studies, the control gro with a placebo, but was just without vitamin D treatment [35,36]. Fo medium risk of bias, this resulted mainly from the randomization pr lection of the reported result [29][30][31][32][33][34], but for two studies was also due the intended interventions [30,31]. The studies for which the high ris cated were within those supporting the positive influence of the supp min D for the psychological measure of depression [35], and those n However, based on the conducted assessment, it should be emphasized four studies supporting the positive influence of vitamin D suppleme chological measure of depression of medium risk of bias [29,[32][33][34] with a medium risk of bias did not support it [30,31]. -Low risk of bias; -Some concerns associated with risk of bias -mains: 1-arising from the randomization process; 2-deviations from the in 3-missing outcome data; 4-measurement of the outcome; 5-selection of th

Discussion
The conducted systematic review did not allow to formulate un sions about influence of the supplementation of vitamin D for the psy of depression, as the various observations were formulated within stu for only two studies, a high risk of bias was intended interventions and in measurement study, also arising from the randomization pro This corresponds the fact that in the indicated with a placebo, but was just without vitamin medium risk of bias, this resulted mainly from lection of the reported result [29][30][31][32][33][34], but for t the intended interventions [30,31]. The studie cated were within those supporting the positi min D for the psychological measure of depr However, based on the conducted assessment four studies supporting the positive influence chological measure of depression of medium with a medium risk of bias did not support it -Low risk of bias; -Some concerns associa mains: 1-arising from the randomization process 3-missing outcome data; 4-measurement of the

Discussion
The conducted systematic review did no sions about influence of the supplementation of depression, as the various observations wer for only two studies, a high risk of bias was defined [35,36] due to deviations from the intended interventions and in measurement of the outcome [35,36], as well as for one study, also arising from the randomization process and due to missing outcome data [35]. This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the selection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not [33] using the revised Cochrane risk-of-bias tool for randomized trials, is presented in Table 5. For the majority of included studies, a medium risk of bias was indicated [29][30][31][32][33][34], while for only two studies, a high risk of bias was defined [35,36] due to deviations from the intended interventions and in measurement of the outcome [35,36], as well as for one study, also arising from the randomization process and due to missing outcome data [35]. This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the selection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not using the revised Cochrane risk-of-bias tool for randomized trials, is presented in Table 5. For the majority of included studies, a medium risk of bias was indicated [29][30][31][32][33][34], while for only two studies, a high risk of bias was defined [35,36] due to deviations from the intended interventions and in measurement of the outcome [35,36], as well as for one study, also arising from the randomization process and due to missing outcome data [35]. This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the se-lection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indi-cated were within those supporting the positive influence of the supplementation of vita-min D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psy-chological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials. -Low risk of bias; -Some concerns associated with risk of bias -High risk of bias; Do-mains: 1-arising from the randomization process; 2-deviations from the intended interventions; 3-missing outcome data; 4-measurement of the outcome; 5-selection of the reported result.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclu-sions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not using the revised Cochrane risk-of-bias tool for randomized trials, is presented in T For the majority of included studies, a medium risk of bias was indicated [29][30][31][32][33][34] for only two studies, a high risk of bias was defined [35,36] due to deviations fro intended interventions and in measurement of the outcome [35,36], as well as f study, also arising from the randomization process and due to missing outcome da This corresponds the fact that in the indicated studies, the control group was not with a placebo, but was just without vitamin D treatment [35,36]. For the studies medium risk of bias, this resulted mainly from the randomization process and in lection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviation the intended interventions [30,31]. The studies for which the high risk of bias wa cated were within those supporting the positive influence of the supplementation o min D for the psychological measure of depression [35], and those not supportin However, based on the conducted assessment, it should be emphasized that there a four studies supporting the positive influence of vitamin D supplementation for th chological measure of depression of medium risk of bias [29,[32][33][34], while two s with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducte the revised Cochrane risk-of-bias tool for randomized trials. -Low risk of bias; -Some concerns associated with risk of bias -High risk of b mains: 1-arising from the randomization process; 2-deviations from the intended interve 3-missing outcome data; 4-measurement of the outcome; 5-selection of the reported res

Discussion
The conducted systematic review did not allow to formulate unambiguous c sions about influence of the supplementation of vitamin D for the psychological m of depression, as the various observations were formulated within studies, which w using the revised Cochrane risk-of-bias tool for randomized trials, is p For the majority of included studies, a medium risk of bias was indic for only two studies, a high risk of bias was defined [35,36] due to d intended interventions and in measurement of the outcome [35,36], study, also arising from the randomization process and due to missing This corresponds the fact that in the indicated studies, the control gro with a placebo, but was just without vitamin D treatment [35,36]. Fo medium risk of bias, this resulted mainly from the randomization pr lection of the reported result [29][30][31][32][33][34], but for two studies was also due the intended interventions [30,31]. The studies for which the high ris cated were within those supporting the positive influence of the supp min D for the psychological measure of depression [35], and those n However, based on the conducted assessment, it should be emphasized four studies supporting the positive influence of vitamin D suppleme chological measure of depression of medium risk of bias [29,[32][33][34] with a medium risk of bias did not support it [30,31]. -Low risk of bias; -Some concerns associated with risk of bias -mains: 1-arising from the randomization process; 2-deviations from the in 3-missing outcome data; 4-measurement of the outcome; 5-selection of th

Discussion
The conducted systematic review did not allow to formulate un sions about influence of the supplementation of vitamin D for the psy of depression, as the various observations were formulated within stu using the revised Cochrane risk-of-bias tool fo For the majority of included studies, a mediu for only two studies, a high risk of bias was intended interventions and in measurement study, also arising from the randomization pro This corresponds the fact that in the indicated with a placebo, but was just without vitamin medium risk of bias, this resulted mainly from lection of the reported result [29][30][31][32][33][34], but for t the intended interventions [30,31]. The studie cated were within those supporting the positi min D for the psychological measure of depr However, based on the conducted assessment four studies supporting the positive influence chological measure of depression of medium with a medium risk of bias did not support it -Low risk of bias; -Some concerns associa mains: 1-arising from the randomization process 3-missing outcome data; 4-measurement of the

Discussion
The conducted systematic review did no sions about influence of the supplementation of depression, as the various observations wer using the revised Cochrane risk-of-bias tool for randomized trials, is presented in Table 5. For the majority of included studies, a medium risk of bias was indicated [29][30][31][32][33][34], while for only two studies, a high risk of bias was defined [35,36] due to deviations from the intended interventions and in measurement of the outcome [35,36], as well as for one study, also arising from the randomization process and due to missing outcome data [35]. This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the selection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not [34] The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials, is presented in Table 5. For the majority of included studies, a medium risk of bias was indicated [29][30][31][32][33][34], while for only two studies, a high risk of bias was defined [35,36] due to deviations from the intended interventions and in measurement of the outcome [35,36], as well as for one study, also arising from the randomization process and due to missing outcome data [35]. This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the selection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials, is presented in Table 5. For the majority of included studies, a medium risk of bias was indicated [29][30][31][32][33][34], while for only two studies, a high risk of bias was defined [35,36] due to deviations from the intended interventions and in measurement of the outcome [35,36], as well as for one study, also arising from the randomization process and due to missing outcome data [35]. This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the se-lection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indi-cated were within those supporting the positive influence of the supplementation of vita-min D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psy-chological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials. -Low risk of bias; -Some concerns associated with risk of bias -High risk of bias; Do-mains: 1-arising from the randomization process; 2-deviations from the intended interventions; 3-missing outcome data; 4-measurement of the outcome; 5-selection of the reported result.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclu-sions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not The risk of bias assessment for studies included to a systematic review, con using the revised Cochrane risk-of-bias tool for randomized trials, is presented in T For the majority of included studies, a medium risk of bias was indicated [29][30][31][32][33][34] for only two studies, a high risk of bias was defined [35,36] due to deviations fro intended interventions and in measurement of the outcome [35,36], as well as f study, also arising from the randomization process and due to missing outcome da This corresponds the fact that in the indicated studies, the control group was not with a placebo, but was just without vitamin D treatment [35,36]. For the studies medium risk of bias, this resulted mainly from the randomization process and in lection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviation the intended interventions [30,31]. The studies for which the high risk of bias wa cated were within those supporting the positive influence of the supplementation o min D for the psychological measure of depression [35], and those not supportin However, based on the conducted assessment, it should be emphasized that there a four studies supporting the positive influence of vitamin D supplementation for th chological measure of depression of medium risk of bias [29,[32][33][34], while two s with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducte the revised Cochrane risk-of-bias tool for randomized trials. -Low risk of bias; -Some concerns associated with risk of bias -High risk of b mains: 1-arising from the randomization process; 2-deviations from the intended interve 3-missing outcome data; 4-measurement of the outcome; 5-selection of the reported res

Discussion
The conducted systematic review did not allow to formulate unambiguous c sions about influence of the supplementation of vitamin D for the psychological m of depression, as the various observations were formulated within studies, which w The risk of bias assessment for studies included to a systematic using the revised Cochrane risk-of-bias tool for randomized trials, is p For the majority of included studies, a medium risk of bias was indic for only two studies, a high risk of bias was defined [35,36] due to d intended interventions and in measurement of the outcome [35,36], study, also arising from the randomization process and due to missing This corresponds the fact that in the indicated studies, the control gro with a placebo, but was just without vitamin D treatment [35,36]. Fo medium risk of bias, this resulted mainly from the randomization pr lection of the reported result [29][30][31][32][33][34], but for two studies was also due the intended interventions [30,31]. The studies for which the high ris cated were within those supporting the positive influence of the supp min D for the psychological measure of depression [35], and those n However, based on the conducted assessment, it should be emphasized four studies supporting the positive influence of vitamin D suppleme chological measure of depression of medium risk of bias [29,[32][33][34] with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic rev the revised Cochrane risk-of-bias tool for randomized trials. -Low risk of bias; -Some concerns associated with risk of bias -mains: 1-arising from the randomization process; 2-deviations from the in 3-missing outcome data; 4-measurement of the outcome; 5-selection of th

Discussion
The conducted systematic review did not allow to formulate un sions about influence of the supplementation of vitamin D for the psy of depression, as the various observations were formulated within stu The risk of bias assessment for studies i using the revised Cochrane risk-of-bias tool fo For the majority of included studies, a mediu for only two studies, a high risk of bias was intended interventions and in measurement study, also arising from the randomization pro This corresponds the fact that in the indicated with a placebo, but was just without vitamin medium risk of bias, this resulted mainly from lection of the reported result [29][30][31][32][33][34], but for t the intended interventions [30,31]. The studie cated were within those supporting the positi min D for the psychological measure of depr However, based on the conducted assessment four studies supporting the positive influence chological measure of depression of medium with a medium risk of bias did not support it -Low risk of bias; -Some concerns associa mains: 1-arising from the randomization process 3-missing outcome data; 4-measurement of the

Discussion
The conducted systematic review did no sions about influence of the supplementation of depression, as the various observations wer The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials, is presented in Table 5. For the majority of included studies, a medium risk of bias was indicated [29][30][31][32][33][34], while for only two studies, a high risk of bias was defined [35,36] due to deviations from the intended interventions and in measurement of the outcome [35,36], as well as for one study, also arising from the randomization process and due to missing outcome data [35]. This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the selection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not [35] cated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not cated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not cated were within those supporting the positive influence of the supplementation o min D for the psychological measure of depression [35], and those not supportin However, based on the conducted assessment, it should be emphasized that there a four studies supporting the positive influence of vitamin D supplementation for th chological measure of depression of medium risk of bias [29,[32][33][34], while two s with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducte the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous c sions about influence of the supplementation of vitamin D for the psychological m of depression, as the various observations were formulated within studies, which w cated were within those supporting the positive influence of the supp min D for the psychological measure of depression [35], and those n However, based on the conducted assessment, it should be emphasized four studies supporting the positive influence of vitamin D suppleme chological measure of depression of medium risk of bias [29,[32][33][34] with a medium risk of bias did not support it [30,31]. -Low risk of bias; -Some concerns associated with risk of bias mains: 1-arising from the randomization process; 2-deviations from the in 3-missing outcome data; 4-measurement of the outcome; 5-selection of th

Discussion
The conducted systematic review did not allow to formulate un sions about influence of the supplementation of vitamin D for the psy of depression, as the various observations were formulated within stu supplementation for the psychological measure of positive influence of vitamin D supplementation fo The risk of bias assessment for studies i using the revised Cochrane risk-of-bias tool fo For the majority of included studies, a mediu for only two studies, a high risk of bias was intended interventions and in measurement study, also arising from the randomization pro This corresponds the fact that in the indicated with a placebo, but was just without vitamin medium risk of bias, this resulted mainly from lection of the reported result [29][30][31][32][33][34], but for t the intended interventions [30,31]. The studie cated were within those supporting the positi min D for the psychological measure of depr However, based on the conducted assessment four studies supporting the positive influence chological measure of depression of medium with a medium risk of bias did not support it -Low risk of bias; -Some concerns associa mains: 1-arising from the randomization process 3-missing outcome data; 4-measurement of the

Discussion
The conducted systematic review did no sions about influence of the supplementation of depression, as the various observations wer cated were within those support min D for the psychological me However, based on the conducte four studies supporting the posi chological measure of depressio with a medium risk of bias did n -Low risk of bias; -Some c mains: 1-arising from the random 3-missing outcome data; 4-measu

Discussion
The conducted systematic r sions about influence of the sup of depression, as the various obs [36] [ 36] 1600 IU of vitamin D3 daily 6 months (HAMD-17) Not confirming * The summary of conclusions defined as confirming (if confirmed positive influence of vitamin D supplementation for the psychological measure of depression) or not confirming (if not confirmed positive influence of vitamin D supplementation for the psychological measure of depression).
The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials, is presented in Table 5. For the majority of included studies, a medium risk of bias was indicated [29][30][31][32][33][34], while for only two studies, a high risk of bias was defined [35,36] due to deviations from the intended interventions and in measurement of the outcome [35,36], as well as for one study, also arising from the randomization process and due to missing outcome data [35]. This corresponds the fact that in the indicated studies, the control group was not treated with a placebo, but was just without vitamin D treatment [35,36]. For the studies with a medium risk of bias, this resulted mainly from the randomization process and in the selection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations from the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not lection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviations the intended interventions [30,31]. The studies for which the high risk of bias was cated were within those supporting the positive influence of the supplementation of min D for the psychological measure of depression [35], and those not supporting However, based on the conducted assessment, it should be emphasized that there are four studies supporting the positive influence of vitamin D supplementation for the chological measure of depression of medium risk of bias [29,[32][33][34], while two st with a medium risk of bias did not support it [30,31]. -Low risk of bias; -Some concerns associated with risk of bias -High risk of bia mains: 1-arising from the randomization process; 2-deviations from the intended interven 3-missing outcome data; 4-measurement of the outcome; 5-selection of the reported resu

Discussion
The conducted systematic review did not allow to formulate unambiguous co sions about influence of the supplementation of vitamin D for the psychological me of depression, as the various observations were formulated within studies, which wa [36] 1600 IU of vitamin D3 daily 6 months (HAMD-17) Not conf * The summary of conclusions defined as confirming (if confirmed positive influence of vit supplementation for the psychological measure of depression) or not confirming (if not con positive influence of vitamin D supplementation for the psychological measure of depressio The risk of bias assessment for studies included to a systematic review, con using the revised Cochrane risk-of-bias tool for randomized trials, is presented in T For the majority of included studies, a medium risk of bias was indicated [29][30][31][32][33][34] for only two studies, a high risk of bias was defined [35,36] due to deviations fro intended interventions and in measurement of the outcome [35,36], as well as f study, also arising from the randomization process and due to missing outcome da This corresponds the fact that in the indicated studies, the control group was not with a placebo, but was just without vitamin D treatment [35,36]. For the studies medium risk of bias, this resulted mainly from the randomization process and in lection of the reported result [29][30][31][32][33][34], but for two studies was also due to deviation the intended interventions [30,31]. The studies for which the high risk of bias wa cated were within those supporting the positive influence of the supplementation o min D for the psychological measure of depression [35], and those not supportin However, based on the conducted assessment, it should be emphasized that there a four studies supporting the positive influence of vitamin D supplementation for th chological measure of depression of medium risk of bias [29,[32][33][34], while two s with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducte the revised Cochrane risk-of-bias tool for randomized trials. -Low risk of bias; -Some concerns associated with risk of bias -High risk of b mains: 1-arising from the randomization process; 2-deviations from the intended interve 3-missing outcome data; 4-measurement of the outcome; 5-selection of the reported res

Discussion
The conducted systematic review did not allow to formulate unambiguous c sions about influence of the supplementation of vitamin D for the psychological m of depression, as the various observations were formulated within studies, which w lection of the reported result [29][30][31][32][33][34], but for two studies was also due the intended interventions [30,31]. The studies for which the high ris cated were within those supporting the positive influence of the supp min D for the psychological measure of depression [35], and those n However, based on the conducted assessment, it should be emphasized four studies supporting the positive influence of vitamin D suppleme chological measure of depression of medium risk of bias [29,[32][33][34] with a medium risk of bias did not support it [30,31]. -Some concerns associated with risk of bias mains: 1-arising from the randomization process; 2-deviations from the in 3-missing outcome data; 4-measurement of the outcome; 5-selection of th

Discussion
The conducted systematic review did not allow to formulate un sions about influence of the supplementation of vitamin D for the psy of depression, as the various observations were formulated within stu [36] 1600 IU of vitamin D3 daily 6 months * The summary of conclusions defined as confirmi supplementation for the psychological measure of positive influence of vitamin D supplementation fo The risk of bias assessment for studies i using the revised Cochrane risk-of-bias tool fo For the majority of included studies, a mediu for only two studies, a high risk of bias was intended interventions and in measurement study, also arising from the randomization pro This corresponds the fact that in the indicated with a placebo, but was just without vitamin medium risk of bias, this resulted mainly from lection of the reported result [29][30][31][32][33][34], but for t the intended interventions [30,31]. The studie cated were within those supporting the positi min D for the psychological measure of depr However, based on the conducted assessment four studies supporting the positive influence chological measure of depression of medium with a medium risk of bias did not support it -Low risk of bias; -Some concerns associa mains: 1-arising from the randomization process 3-missing outcome data; 4-measurement of the

Discussion
The conducted systematic review did no sions about influence of the supplementation of depression, as the various observations wer lection of the reported result [29][30][31][32][33][34], but fo the intended interventions [30,31]. The stu cated were within those supporting the pos min D for the psychological measure of de However, based on the conducted assessme four studies supporting the positive influen chological measure of depression of mediu with a medium risk of bias did not support -Some concerns asso mains: 1-arising from the randomization proce 3-missing outcome data; 4-measurement of th

Discussion
The conducted systematic review did sions about influence of the supplementatio of depression, as the various observations w the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not associated with the studied group, sample size, or studied effect. Despite that, for two studies of major depressive disorders, the positive effect of vitamin D was indicated [29,35]; one of them was defined as associated with the high risk of bias [35], so it does not allow us to extrapolate. It may indicate that there was only one study of postpartum depression defined as associated with a medium risk of bias that confirmed the positive influence of vitamin D, which may be promising [34].
Taking into account the observations from the included studies, the potential mechanism of influence of vitamin D on depression must be considered. However, the current knowledge about the effect of vitamin D on neuronal brain functioning and behaviors is based on animal studies, as little is known based on human studies so far [37]. The association between vitamin D and depression is probably associated with the fact that vitamin D receptors are not only present, but even widespread, in the hippocampus and other brain areas implicated in depression [38]. At the same time, vitamin D metabolites are able to cross the blood-brain barrier, which allows them to act -Low risk of bias; the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not associated with the studied group, sample size, or studied effect. Despite that, for two studies of major depressive disorders, the positive effect of vitamin D was indicated [29,35]; one of them was defined as associated with the high risk of bias [35], so it does not allow us to extrapolate. It may indicate that there was only one study of postpartum depression defined as associated with a medium risk of bias that confirmed the positive influence of vitamin D, which may be promising [34].
Taking into account the observations from the included studies, the potential mechanism of influence of vitamin D on depression must be considered. However, the current knowledge about the effect of vitamin D on neuronal brain functioning and behaviors is based on animal studies, as little is known based on human studies so far [37]. The association between vitamin D and depression is probably associated with the fact that vitamin D receptors are not only present, but even widespread, in the hippocampus and other brain areas implicated in depression [38]. At the same time, vitamin D metabolites are able to cross the blood-brain barrier, which allows them to act -Some concerns associated with risk of bias the intended interventions [30,31]. The studies for which the high risk of bias was indicated were within those supporting the positive influence of the supplementation of vitamin D for the psychological measure of depression [35], and those not supporting [36]. However, based on the conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias [29,[32][33][34], while two studies with a medium risk of bias did not support it [30,31]. Table 5. The risk of bias assessment for studies included to a systematic review, conducted using the revised Cochrane risk-of-bias tool for randomized trials.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not associated with the studied group, sample size, or studied effect. Despite that, for two studies of major depressive disorders, the positive effect of vitamin D was indicated [29,35]; one of them was defined as associated with the high risk of bias [35], so it does not allow us to extrapolate. It may indicate that there was only one study of postpartum depression defined as associated with a medium risk of bias that confirmed the positive influence of vitamin D, which may be promising [34].
Taking into account the observations from the included studies, the potential mechanism of influence of vitamin D on depression must be considered. However, the current knowledge about the effect of vitamin D on neuronal brain functioning and behaviors is based on animal studies, as little is known based on human studies so far [37]. The association between vitamin D and depression is probably associated with the fact that vitamin D receptors are not only present, but even widespread, in the hippocampus and other brain areas implicated in depression [38]. At the same time, vitamin D metabolites are able to cross the blood-brain barrier, which allows them to act -High risk of bias; Domains: 1-arising from the randomization process; 2-deviations from the intended interventions; 3-missing outcome data; 4-measurement of the outcome; 5-selection of the reported result.

Discussion
The conducted systematic review did not allow to formulate unambiguous conclusions about influence of the supplementation of vitamin D for the psychological measure of depression, as the various observations were formulated within studies, which was not associated with the studied group, sample size, or studied effect. Despite that, for two studies of major depressive disorders, the positive effect of vitamin D was indicated [29,35]; one of them was defined as associated with the high risk of bias [35], so it does not allow us to extrapolate. It may indicate that there was only one study of postpartum depression defined as associated with a medium risk of bias that confirmed the positive influence of vitamin D, which may be promising [34].
Taking into account the observations from the included studies, the potential mechanism of influence of vitamin D on depression must be considered. However, the current knowledge about the effect of vitamin D on neuronal brain functioning and behaviors is based on animal studies, as little is known based on human studies so far [37]. The association between vitamin D and depression is probably associated with the fact that vitamin D receptors are not only present, but even widespread, in the hippocampus and other brain areas implicated in depression [38]. At the same time, vitamin D metabolites are able to cross the blood-brain barrier, which allows them to act there [39], as well as in vitro and in vivo studies in animal models revealed that vitamin D deficiency may influence the shape or function of the hippocampal development [40]. Similarly, the human studies indicated that vitamin D deficiency is associated with decreased brain tissue and hippocampal volume, detected during brain magnetic resonance imaging (MRI) [41].
In general, vitamin D is a neuroactive steroid which contributes to the expression of neurotransmitters with its regulation and neuroimmunomodulation, antioxidant production, and various neurotrophic factors [40]. It may also upregulate genes involved in the synthesis of tyrosine hydroxylase, being an enzyme involved in the synthesis of catecholamines [42] that is potentially involved in depression development and treatment [43]. All indicated actions of vitamin D may participate in the mechanism of depression treatment and prevention, but the question arises as to whether they are significant enough to participate in treatment, or only in prevention. The role of vitamin D is generally indicated as protective [37] by potential reducing of the negative effects of dopaminergic toxins, possibly by increasing glial cell-line-derived neurotrophic factor and affecting serotonin transmission in the brain, linking dopaminergic and serotonergic systems [44,45]. Similarly, the preventive role of vitamin D is confirmed by the recent meta-analysis of RCTs by Xie et al. [46], which indicated its beneficial impact on the incidence of depression.
At the same time, for the treatment, the results are not unambiguous as various studies provide diverse observations and conclusions. While more human studies are needed to make a conclusion, the quality of the necessary studies should be emphasized, as not only RCTs should be conducted, but they should be rigorously planned and executed.
Moreover, it should be emphasized that there is also a need to assess the influence of vitamin D on depression in children and adolescents, which should be the aim of the further studies. So far, it may be indicated that-similarly as for adults-the results are not unambiguous here. In the RCT by Libuda et al. [47] for adolescents with vitamin D deficiency and at least mild depression, the study failed to prove a vitamin D supplementation effect on self-rated depression, but parents of the treated adolescents reported fewer depressive symptoms in their progeny.
As revealed within the presented systematic review, the quality of included studies is the major problem. An important problem is also the need for placebo-based studies (instead of studies with control group without placebo), which are especially important for such a condition as depression, as the effectiveness of the placebo is proven to increase the effect of cognitive-behavioral therapy in depressive patients [48]. Taking this into account, not receiving any treatment within the study may contribute to seeking other therapeutic options, or to reduced effectiveness of the standard therapy as a result of the feeling of deprivation [49]. The other limitation of the conducted study results from a heterogeneity of included studies, using the various psychological measures of depression and studying various populations. As the conducted systematic review presents only the limited number of studies published so far, while included studies presented various studied groups, outcomes, and psychological measures, more studies are necessary to deepen the observations. Moreover, since the studies assessed a wide range of possible psychological measures, meta-analysis was impossible [50], so only the systematic review was conducted.

Conclusions
Based on the conducted assessment, there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of medium risk of bias, while two studies with a medium risk of bias did not support it. Taking this into account, the conducted systematic review is not a strong confirmation of the effectiveness of vitamin D supplementation in the treatment of depression.
Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 .3390/nu15040951/s1, Table S1: The detailed electronic search strategy applied for the systematic review within PubMed or Web of Science databases; Table S2: The observations and conclusions formulated within studies included to a systematic review.  Institutional Review Board Statement: The literature search was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42020155779).

Conflicts of Interest:
The authors declare no conflict of interest.